Alexander Trinks (Jena, DE), Patricia Radon (Berlin, DE), Swanti Schapp (Jena, DE), Diana Zahn (Ilmenau, DE), Dr. Frank Wiekhorst (Berlin, DE), Professor Silvio Dutz (Ilmenau, DE; Zwickau, DE), Professor Andreas Hochhaus (Jena, DE), Dr. Joachim Clement (Jena, DE)
Abstract text (incl. figure legends and references)
Introduction The biomedical application of nanomaterials is growing with a strong need to understand the interaction between nanomaterials and the human body. Since clinical trials on pregnant women are difficult to perform, physiologically appropriate models of the human placenta to study nanoparticle-placenta interactions in vitro are needed.
Objectives We aim to gain a better understanding of the interactions of magnetic nanoparticles (MNP), with the blood-placenta barrier. In this study, we investigated how the fusion of cytotrophoblasts to syncytiotrophoblasts affects the involved pericytes and the passage of MNPs through the barrier.
Methods The in vitro BPB was established in a microfluidic chip by using the cytotrophoblast cell line BeWo on the apical (maternal) side and human primary placental pericytes on the basolateral (fetal) side. Differentiation of the BeWo cells was induced by a 24h-incubation with 20 µM forskolin. Barrier integrity was verified by sodium-fluorescein (Na-Flu) permeability. The forskolin-induced changes were confirmed by fluorescence microscopy and qPCR. Citrate-coated MNP (hydrodynamic diameter 116 nm, z-potential -35 mV) were applied for 24 h. For quantification of the MNP content magnetic particle spectroscopy (MPS) was performed.
Results Na-Flu incubation showed a 5-fold reduction in permeability for cell-covered barriers compared to empty ones. Forskolin caused a 3.6-fold increase of chorion gonadotropin expression. After forskolin and MNP incubation the distribution of MNPs in the apical and basolateral compartment as well as in the cell layer was determined by MPS. The formation of syncytiotrophoblasts did not affect the penetration rate of MNPs. In the basolateral compartment, no significant difference in MNP content was measured before forskolin addition (2.3% ± 2.0%) and after cytotrophoblast fusion (2.4% ± 1.6%).
Conclusion We demonstrate that MNPs pass a cytotrophoblastic cell layer as well as a syncytiotrophoblast.